The article by Paul P. Tak and Gary S. Firestein discusses the central role of the NF-κB/Rel transcription family in inflammation and inflammatory diseases. NF-κB activation, driven by nuclear translocation of cytoplasmic complexes, is crucial for the induction of proinflammatory genes. The authors highlight the specificity of various NF-κB proteins, their roles in immune responses, and the regulation of NF-κB activity by IκB proteins and IκB kinase (IKK). They also explore therapeutic strategies aimed at inhibiting NF-κB, including the use of IKK-β dominant-negative gene therapy and specific NF-κB inhibitors. The article reviews the activation of NF-κB in animal models of inflammation, such as collagen-induced arthritis and asthma, and its implications in human inflammatory diseases like rheumatoid arthritis, asthma, and inflammatory bowel disease. The authors emphasize the potential of targeting specific NF-κB subunits, IκB proteins, or kinases to achieve therapeutic efficacy while minimizing systemic toxicity.The article by Paul P. Tak and Gary S. Firestein discusses the central role of the NF-κB/Rel transcription family in inflammation and inflammatory diseases. NF-κB activation, driven by nuclear translocation of cytoplasmic complexes, is crucial for the induction of proinflammatory genes. The authors highlight the specificity of various NF-κB proteins, their roles in immune responses, and the regulation of NF-κB activity by IκB proteins and IκB kinase (IKK). They also explore therapeutic strategies aimed at inhibiting NF-κB, including the use of IKK-β dominant-negative gene therapy and specific NF-κB inhibitors. The article reviews the activation of NF-κB in animal models of inflammation, such as collagen-induced arthritis and asthma, and its implications in human inflammatory diseases like rheumatoid arthritis, asthma, and inflammatory bowel disease. The authors emphasize the potential of targeting specific NF-κB subunits, IκB proteins, or kinases to achieve therapeutic efficacy while minimizing systemic toxicity.